Vitamin B6 (pyridoxal-5'-phosphate [PLP]) is a cofactor in over 100 enzymatic reactions involving protein, DNA, and energy metabolism. Plasma PLP is reduced in patients with rheumatoid arthritis (RA). Recently, we have found that patients with RA and low PLP also have elevated homocysteine levels, both fasting and in response to an oral methionine challange than do healthy subjects. Hyper-homocysteinemia is a newly recognized risk factor for stroke and coronary heart disease, and may be important in explaining the increased mortality rate of patients with RA.